This invention relates to a process for the preparation of 4-arylthioanilines of the formula ##STR1## wherein A is halogen or CF.sub.3 and B is hydrogen or halogen from 4-unsubstituted anilines of the formula ##STR2##
The products I can be converted directly to the corresponding 4-phenylthioalkanesulfonanilides of the formula ##STR3## wherein A and B are as previously defined and R can be an alkyl group containing from 1 to 4 carbon atoms or monohalomethyl. These compounds (III) are known herbicidal and plant growth modifying agents. Thus, see U.S. Pat. No. 3,948,987 and British patent application No. 8002852 (filed Jan. 28, 1980, published Sept. 10, 1980 under Ser. No. 2,041,369A and corresponding to U.S. application Ser. No. 7,026 filed Jan. 29, 1979).
The present invention relates to a process for the preparation of 4-arylthioanilines of the formula ##STR4## wherein A is halogen or trifluoromethyl and B is hydrogen or halogen which comprises
(1) reacting a substituted aniline of the formula ##STR5## with an alkali metal thiocyanate in the presence of halogen to provide the corresponding 4-thiocyanoaniline: ##STR6## (2) mixing a solution of that compound in a solvent with a concentrated aqueous alkali metal sulfide solution to form the corresponding alkali metal mercaptide ##STR7## wherein M is an alkali metal atom; (3) heating the reaction mixture containing the alkali metal mercaptide with cuprous oxide to form the cuprous mercaptide salt ##STR8## in situ; and (4) treating the heated reaction mixture with an aryl halide to form the desired product.
A particularly valuable aspect of the invention relates to the process of steps (2), (3) and (4), supra, for reasons given hereinafter.
This process offers advantages in the availability and cost of precursors over the known processes for the preparation of compounds III (shown in the patents just cited) and in overall high yield. In addition, the process is easily carried out at moderate temperatures, at atmospheric pressure (if desired) and without special production equipment.
The process can be characterized schematically as follows ##STR9##
Normal molar proportions of the reactants can be utilized, although excesses of particular materials are often utilized to maximize yields. A less than molar proportion of cuprous oxide can be utilized when steps (3) and (4) are being carried out together in the reaction mixture since cuprous ion is released when the reaction of step (4) takes place thus releasing it for reuse in step (3). The amount of solvent is generally adjusted to achieve total solubility of the reactants under the conditions being utilized.
The starting materials for step (1) are, in general, commercially available. The thiocyanation is para-directing with respect to the amine group in the precursor and halo and CF.sub.3 substituents on the other ring positions do not interfere with the reaction, which normally occurs in high yields, sometimes approaching theoretical. Conveniently, a solution of the precursor analine and an excess of sodium or potassium thiocyanate in methanol is mixed with bromine or chlorine. The temperature is maintained in the range of about 0.degree.-45.degree. C. in order to maintain solution of the reactants. When chlorine is utilized in this step, the gas is ordinarily passed directly into the solution while bromine is added dropwise. Alternatively, a solution of bromine in methanol saturated with sodium bromide can be added dropwise to the aniline-thiocyanate solution. When the reaction is substantially complete, the mixture is neutralized and the solid substituted 4-thiocyanoaniline product is collected, purified and dried.
Steps (2), (3) and (4) are preferably carried out in the same reaction vessel without removing or separating the constituents until the final product (I) has been prepared (although this is not necessary). Step (2) involves the formation of the alkali metal (sodium or potassium) mercaptide from the thiocyanoaniline, preferably by adding a solution of the latter in dimethylformamide to a concentrated solution of the alkali metal sulfide in water. The reaction is advantageously run in an inert atmosphere and is warmed for a time, e.g., at about 50.degree. C.
Steps (3) and (4) are ordinarily carried out together by heating the aqueous dimethylformamide solution, normally at the reflux temperature of the mixture (in the range of about 150.degree.-170.degree. C. in most cases) for several hours with cuprous oxide and an excess of an aryl halide, preferably iodobenzene or bromobenzene to maximize the yield.
The dimethylformamide (which is the normally preferred solvent) can if desired be replaced by dimethyl sulfoxide or by a mixture of quinoline and pyridine. The solvent is chosen to boil in the range of about 150.degree.-170.degree. C.
Although the reagents for steps (3) and (4) may be added at the same time, the reactions themselves take place in order, and if the cuprous oxide is omitted the desired 4-phenylthioaniline is not formed. However, when carried out as described herein, the overall yields of steps (2), (3) and (4) is ordinarily very high, often approaching quantitative.